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Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s P rogrammes at the University of Pécs and at the University of Debrecen Identification number : TÁMOP-4.1.2-08/1/A-2009-0011. - PowerPoint PPT Presentation
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Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011
CLINICAL TRIALS (3)
Dr. Judit PongráczThree dimensional tissue cultures and tissue engineering – Lecture 25
Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011
TÁMOP-4.1.2-08/1/A-2009-0011
Tissue engineered blood vessel• TE blood vessels are used only in low pressure pulmonary
circulation• These grafts are not durable enough to withstand high arterial
pressure
Small-veinharvest
Cell seedingon polymer
Cell isolation
Cell expansion
Tissue-engineered graft
TÁMOP-4.1.2-08/1/A-2009-0011
TEBV production• A completely biological tissue-engineered
human blood vessel (Nicolas L'heureux, Stéphanie Pâquet, Raymond Labbé, Lucie Germain, and François A. Auger ) FASEB Journal 1998
• HUVEC and SMC were used
TÁMOP-4.1.2-08/1/A-2009-0011
Myocardial infaction• Stem cells are used in cases following
extensive damage• In most cases improvement is shown but
further studies are needed
TÁMOP-4.1.2-08/1/A-2009-0011
Urethra and bladder• Acellular collagen-based matrices• Intestinal or bladder epithelial cells• 4-7 years later 34 out of 40 patients had a
successful outcome
TÁMOP-4.1.2-08/1/A-2009-0011
Cartilage• Two multicentre clinical trials• In most cases improvement was noted• Long term effects are still being considered
TÁMOP-4.1.2-08/1/A-2009-0011
Lung
TÁMOP-4.1.2-08/1/A-2009-0011
Trachea - bronchi - lungs
TÁMOP-4.1.2-08/1/A-2009-0011
Lung diseases benefiting from cell based therapies• COPD (chronic obstuctive pulmonary disease)• ARDS (acute respiratory distress syndrome)• Asthma• Mechanical tissue damages
TÁMOP-4.1.2-08/1/A-2009-0011
Strategies for cell-based therapies for the lung
Pulmonary epithelial-like cells
Embryonic stem cells
Culture
Selection(genetic, air liquid interface, media co-culture)
Epithelium Vasculature
Stroma (fibroblast)
ESCs, MSCs, Fibrocytes
Acute cytoprotection/repair(survival, growth factors)
Cartilage
Intratracheal/Vascular infusionStructural grafts
Engraftment Gene transferDelivery of therapeutic
molecules
Engraftment
Organoid
Functional unit
Endothelium
Pulmonary epithelium
Mesenchyme
TÁMOP-4.1.2-08/1/A-2009-0011
Complexity of lung structures during development
Columnar cells
Fibroblasts
Goblet cell
Basal cell
Ciliated cellClara cell Type I cell
Type IIcell
I.Embryonic
E 9-12
II.Pseudoglandular
E 12-15
III.CanalicularE 15-E17
IV.Saccular
E 17-Birth
V.Alveolar
Birth-PN20
Lung budEs Es
T T
RESEARCH APPLICATION AND DRUG TESTING
Dr. Judit PongráczThree dimensional tissue cultures and tissue engineering – Lecture 26
Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011
TÁMOP-4.1.2-08/1/A-2009-0011
Research applications• Intercellular interaction• Study of Signaling pathway (inter and intra-
cellular)• Study of regeneration processes• Modeling diseases
TÁMOP-4.1.2-08/1/A-2009-0011
Thymus reaggregation
E15 mouse embryo
T-lymphocytes orlymphoid progenitors
Deoxiguanosine cultures
Thymic epithelial cells
E15 thymic lobes
Reaggregate
TÁMOP-4.1.2-08/1/A-2009-0011
Thymocyte development in the reaggregated thymus
Intracellular Notch(ICN)
• No T-cell commitment• Allows B-cell commitment
• Induces T-cell commitment• Blocks B-cell commitment
Nucleus
Stromal cell
Lymphocyte progenitor
Jagged/Delta-like
CSLCSLCoR CoA
Preseniling-Secretase
CoR
(ICN)
TÁMOP-4.1.2-08/1/A-2009-0011
Salivary gland aggregate
GFP-Ad FoxN1-Ad
TÁMOP-4.1.2-08/1/A-2009-0011
Tissue specific changes• Expression of transcription factors and other
genes are easily modified• Gene expression modification is tissue type
restricted• Effects on the whole tissue can be studied at
the level of morphology, cellular interactions and signaling
TÁMOP-4.1.2-08/1/A-2009-0011
Drug testing• Toxicity testing• Efficacy testing
TÁMOP-4.1.2-08/1/A-2009-0011
Hepatotoxicity testing• Purified primary human hepatocytes in 2D• Complex 3D liver micro-tissues for toxicity• Toxicity testing (acute and chronic)• Viability assays• Bile production• Molecular marker tests (albumin etc)
TÁMOP-4.1.2-08/1/A-2009-0011
Lung model for drug testing• Complex cellular composition• Close to physiological drug transporter expression• Easy handling• Suitability for HTS
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